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The Toll pathway inhibits tissue growth and regulates cell fitness in an infection-dependent manner

The Toll pathway regulates the cellular response to infection via the transcriptional upregulation of antimicrobial peptides. In Drosophila, apart from its role in innate immunity, this pathway has also been reported to be important for the elimination of loser cells in a process referred to as cell...

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Autores principales: Germani, Federico, Hain, Daniel, Sternlicht, Denise, Moreno, Eduardo, Basler, Konrad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279345/
https://www.ncbi.nlm.nih.gov/pubmed/30451683
http://dx.doi.org/10.7554/eLife.39939
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author Germani, Federico
Hain, Daniel
Sternlicht, Denise
Moreno, Eduardo
Basler, Konrad
author_facet Germani, Federico
Hain, Daniel
Sternlicht, Denise
Moreno, Eduardo
Basler, Konrad
author_sort Germani, Federico
collection PubMed
description The Toll pathway regulates the cellular response to infection via the transcriptional upregulation of antimicrobial peptides. In Drosophila, apart from its role in innate immunity, this pathway has also been reported to be important for the elimination of loser cells in a process referred to as cell competition, which can be locally triggered by secreted factors released from winner cells. In this work, we provide evidence that the inhibition of Toll signaling not only increases the fitness of loser cells, but also bestows a clonal growth advantage on wild-type cells. We further demonstrate that this growth advantage depends on basal infection levels since it is no longer present under axenic conditions but exacerbated upon intense pathogen exposure. Thus, the Toll pathway functions as a fine-tuned pro-apoptotic and anti-proliferative regulator, underlining the existence of a trade-off between innate immunity and growth during development.
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spelling pubmed-62793452018-12-05 The Toll pathway inhibits tissue growth and regulates cell fitness in an infection-dependent manner Germani, Federico Hain, Daniel Sternlicht, Denise Moreno, Eduardo Basler, Konrad eLife Developmental Biology The Toll pathway regulates the cellular response to infection via the transcriptional upregulation of antimicrobial peptides. In Drosophila, apart from its role in innate immunity, this pathway has also been reported to be important for the elimination of loser cells in a process referred to as cell competition, which can be locally triggered by secreted factors released from winner cells. In this work, we provide evidence that the inhibition of Toll signaling not only increases the fitness of loser cells, but also bestows a clonal growth advantage on wild-type cells. We further demonstrate that this growth advantage depends on basal infection levels since it is no longer present under axenic conditions but exacerbated upon intense pathogen exposure. Thus, the Toll pathway functions as a fine-tuned pro-apoptotic and anti-proliferative regulator, underlining the existence of a trade-off between innate immunity and growth during development. eLife Sciences Publications, Ltd 2018-11-19 /pmc/articles/PMC6279345/ /pubmed/30451683 http://dx.doi.org/10.7554/eLife.39939 Text en © 2018, Germani et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Developmental Biology
Germani, Federico
Hain, Daniel
Sternlicht, Denise
Moreno, Eduardo
Basler, Konrad
The Toll pathway inhibits tissue growth and regulates cell fitness in an infection-dependent manner
title The Toll pathway inhibits tissue growth and regulates cell fitness in an infection-dependent manner
title_full The Toll pathway inhibits tissue growth and regulates cell fitness in an infection-dependent manner
title_fullStr The Toll pathway inhibits tissue growth and regulates cell fitness in an infection-dependent manner
title_full_unstemmed The Toll pathway inhibits tissue growth and regulates cell fitness in an infection-dependent manner
title_short The Toll pathway inhibits tissue growth and regulates cell fitness in an infection-dependent manner
title_sort toll pathway inhibits tissue growth and regulates cell fitness in an infection-dependent manner
topic Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279345/
https://www.ncbi.nlm.nih.gov/pubmed/30451683
http://dx.doi.org/10.7554/eLife.39939
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